Screening drugs and compounds to fight against Cronobacter sakazakii (C. sakazakii), one of the most common pathogens that can cause fatal necrotizing enterocolitis, septicema and meningitis, is still needed. We found that p-coumaric acid (pCA) has an inhibitory effect on C. sakazakii in vitro and in vivo. Proteomic changes of C. sakazakii BAA-894 exposed to pCA were studied to reveal the antibacterial mechanisms involved. A total of 1,553 proteins were identified in C. sakazakii BAA-894 by label-free proteomics analysis. Fuzzy cluster analysis showed that 33 were up-regulated, and 110 were down-regulated with pCA treatment. Gene Ontology (GO) analysis concluded that pCA caused the change of metabolic state of bacteria and generally in the state of metabolic inhibition. KEGG Enrichment Analysis (KEGG) analysis showed that pCA inhibited energy metabolism and distorted the balance of amino acid metabolism. Posttranslational modification analysis showed that pCA affected the deamidation of three proteins, including Elongation factor Tu, one of the vital proteins in bacteria. Molecular docking suggested the hydrogen bond between the pCA carboxyl group and Elongation factor Tu Asn-64 might contribute to deamidation. Overall, we found that pCA interfered with cellular energy and amino acid metabolism and promoted elongation factor Tu deamidation, suggesting that pCA can be an effective natural substitute to control C. sakazakii.
Bo Yang,Bowen Wang,Guoliang Wang,Wenliang Cao,Qian Wang,Hao Pu,Wei An
Background: P-coumaric acid (p-CA) is a kind of phenylpropionic acid derived from aromatic amino acids, which is widely distributed in many plants and human diets. It has strong pharmacological and inhibitory effects on a variety of tumors. However, the role of p-CA in osteosarcoma, a tumor with a poor prognosis, is still unknown. Therefore, we aimed to evaluate the effect of p-CA on osteosarcoma and explore its potential mechanism. Objective: This study aimed to investigate whether p-CA has an inhibitory effect on the growth of osteosarcoma cells and explore its potential mechanism. Methods: MTT assay and clonogenic assay were used to detect the effect of p-CA on the proliferation of osteosarcoma cells. The effect of p-CA on apoptosis of osteosarcoma cells was detected by the Hoechst staining and flow cytometry. The effects of p-CA on the migration and invasion of osteosarcoma cells were detected by scratch healing assay and Transwell invasion assay. Western blot and PI3K/Akt pathway activator 740Y-P were used to detect the anti-tumor mechanism of p-CA on osteosarcoma cells. The effect of p-CA on osteosarcoma cells in vivo was verified by an orthotopic osteosarcoma tumor animal model in nude mice. Results: MTT assay and clonogenic assay showed that p-CA inhibited the proliferation of osteosarcoma cells. Hoechst stain and flow cytometry showed that p-CA could induce apoptosis of osteosarcoma cells and lead to G2 phase arrest of osteosarcoma cells. Transwell assay and scratch healing assay found that p-CA could inhibit the migration and invasion of osteosarcoma cells. Western blot showed that p-CA could inhibit the activity of the PI3K/Akt signaling pathway in osteosarcoma cells, and 740Y-P could reverse its inhibitory effect. In vivo mouse models, p-CA has an antitumor effect on osteosarcoma cells in vivo, and at the same time, it has less toxic side effects on mice. Conclusion: This study demonstrated that p-CA could effectively inhibit the proliferation, migration and invasion of osteosarcoma cells and promote apoptosis. p-CA may play an anti-osteosarcoma role by inhibiting PI3K/Akt signaling pathway.
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